RTTNews) - Exelixis, Inc. (EXEL: News ) Saturday revealed data from two ongoing clinical studies exploring lower starting doses of its cancer drug cabozantinib.
The company elaborated on the phase 1 investigator-sponsored trial, or IST, to assess the lowest effective dose of cabozantinib for treatment of metastatic bone lesions in patients with metastatic castration-resistant prostate cancer, or CRPC, as assessed by post-treatment changes in bone scans.
Preliminary data showed that a daily starting dose of 40 mg resulted in high rates of bone scan response assessed by computer-aided detection by an independent radiology facility in men with CRPC and bone metastases.
The 40 mg dose was also associated with improved tolerability compared with the 100 mg daily dose used in the ongoing phase 2 randomized discontinuation trial of cabozantinib.
Richard Lee, Instructor in Medicine at the Massachusetts General Hospital Cancer Center, will present the data from the IST tomorrow in a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in San Francisco.
Elaborating on bone scan results, Exelixis said the study enrolled 23 patients. Bone scan response at week 6 is the primary endpoint of this study and is defined as a =30% reduction in the bone scan lesion area on the week 6 bone scan relative to baseline as assessed by a CAD system at an independent radiology facility .
Twelve patients were enrolled in the 40 mg cohort. One of the these patients discontinued the study at Week 2 due to worsening of pre-existing anorexia and fatigue, and another patient discontinued at Week 6 after experiencing a pathologic hip fracture.
Eleven patients were evaluable at Week 6, of which 10 had bone scan responses. The median decrease in bone scan lesion area was 61.5%. Eight of the 10 responding patients had a confirmation of the bone scan response at week 12 and continue on treatment with a median duration of treatment of 19 weeks.
Based on the bone scan findings of the 40 mg cohort, a second cohort of 11 patients was enrolled and is receiving cabozantinib at a dose of 20 mg daily. Nine of these patients were evaluable at 6 weeks, of which two had a bone scan response. Six other patients had stable diseaseby bone scan, and one patient had progressive disease by bone scan.
Exelixis sadi that based on the results to date in the 20 mg and 40 mg cohorts, an expanded cohort of 13 patients at the 40 mg daily dose is expected to
open shortly.
Daily cabozantinib at 40 mg or below was well tolerated. There were no dose reductions or interruptions during the first 12 weeks for the 40 mg cohort and during the first 6 weeks in the 20 mg cohort. A single patient in the 40 mg cohort experienced =Grade 3 drug-related adverse events of worsening of pre-existing anorexia) and fatigue and discontinued study treatment at week 2.
Post Edited (robertcool) : 11/12/2011 1:37:08 PM (GMT-7)